In 1977, Miller, et al., did studies with bullfrogs and found that the pigment epithelium actively secretes sodium and calcium into the retinal space and absorbs chlorine and perhaps bicarbonate and potassium, and that this activity could be important in controlling the ionic milieu in the outer retina. Miller, et al., "Active Transport of Ions Across Frog Retinal Pigment Epithelium," Experimental Eye Research, 25:235-248 (1977).
In 1982, Marmor, et al. suggested that acetazolamide (intravenous) might have application in preventing or slowing the spread of retinal detachments or hasten resorption of subretinal fluid. Marmor, et al., "Enhancement of Retinal Adhesion and Subretinal Fluid Resorption by Acetazolamide," Investigative Ophthalmology, 23 (1):121-124 (July, 1982). In 1986, it was found that acetazolamide in high doses enhanced subretinal fluid resorption, but had little effect when dosed as ordinarily used. Marmor, et al., "Pharmacologic Modification of Subretinal Fluid Absorption in the Rabbit Eye," Archives of Ophthalmology, 104:1674-1677 (Nov. 1986). Clinical studies in 1988 showed that acetazolamide modifies or causes resolution of macular edema in some patients. The studies showed no detectable effect on macular edema due to primary retinal vascular disease in contrast to the macular edema resulting from inflammation or inherited outer retinal disorders. Cox, et al, "Treatment of Chronic Macular Edema With Acetazolamide," Archives of Ophthalmology, 106:1190-1194 (September 1988). In 1994, Borhani et al., suggested the intraocular administration (injection) of acetazolamide for treating cystoid macular edema rather that systemic administration due to the serious systemic side effects associated with systemic administration. Borhani, et al., "Vitreoretinal Toxicity of Acetazolamide Following Intravitreal Administration in the Rabbit Eye," Ophthalmic Surgery, 25 (3):166-169 (March 1994).
Brinzolamide is disclosed in commonly assigned U.S. Pat. Nos. 5,240,923 and 5,378,703 for its usefulness in controlling intraocular pressure, particularly in the treatment of glaucoma. These patents are incorporated herein by reference.
Retinal edema is treated today with non-steroidal anti-inflammatories, corticosteroids, laser photocoagulation, and systemic acetazolamide. The use of brinzolamide provides an alternative drug for the treatment of this prevalent condition.